Reactive oxygen species (ROS) are toxic byproducts of energy production in the mitochondria. "Oxidative stress" is the constant barrage of oxidative damage which ROS inflict upon DNA, proteins, lipids and other biologically important molecules (1,2) (FIG. 1). Oxidative stress has been implicated as a pathologic mechanism in aging and several diseases (3,4,5). Consequently, oxygen is now recognized as both beneficial and harmful: it is essential to sustain mammalian life because it is the final acceptor of electrons in oxidative metabolism, but in this process it also causes oxidative stress and tissue damage.
Although the significance of oxidative stress in disease is well recognized, it has proved difficult to measure its intensity in vivo. Various markers have been proposed, including malonaldehyde and conjugated dienes in the blood, and hydrocarbons and hydrogen peroxide in the breath (6,7). Breath markers of oxidative stress have attracted attention because breath tests are intrinsically non-invasive and painless (8). Increased breath alkanes, particularly ethane and pentane, have demonstrated increased oxidative stress in breast cancer (9), rheumatoid arthritis (10), heart transplant rejection (11), acute myocardial infarction (12), schizophrenia (13) and bronchial asthma (14).
However, breath tests for ethane and pentane have limited value in screening for these disorders because their sensitivity and specificity are poor, resulting in large numbers of false positive and false negative results.
Oxidative stress produces many different degradation products, so that ethane and pentane are only one-dimensional markers of a larger process. Phillips et al recently reported a two-dimensional marker of oxidative stress, the breath alkane profile (U.S. application Ser. No. 09/229,020: A breath test for the detection of various diseases). This marker comprises the alveolar gradient (concentration in breath minus concentration in air) of a spectrum of alkanes from C4 to C20. The alveolar gradient varies with the difference between the rate of synthesis and the rate of clearance of a volatile organic compound (VOC) in the body. In a group of normal humans, the breath alkane profile was found to rise significantly with age.
Phillips et al also previously observed that methylated alkanes are common components of the breath in normal humans as well as in those suffering from lung cancer (15,16). These VOCs appeared to provide additional markers of oxidative stress.